Trial Outcomes & Findings for Tapentadol in Chronic Malignant Tumour Related Pain (NCT NCT01264887)

Last Updated: 2019-11-04

Results Overview

The severity of treatment emergent adverse events was any untoward medical occurrence in a patient administered tapentadol. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of the (investigational) medicinal product whether or not related to the use of tapentadol. The clinical "intensity" of adverse event were classified as: Mild: signs and symptoms which can be easily tolerated. Symptoms could be ignored and disappeared when the participant is distracted. Moderate: symptoms caused discomfort but were tolerable, they could not be ignored and affect concentration. Severe: symptoms affected the usual daily activity.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

31 participants

Primary outcome timeframe

Day 1; up to 144 weeks

Results posted on

2019-11-04

Participant Flow

First participant was enrolled on the 03 March 2011 and the last participant completed the trial on the 08 May 2014.

Participant milestones

Participant milestones
Measure	Tapentadol Prolonged Release All participants from the KF5503/15 that enrolled into this trial were on tapentadol prolonged release. Participants were dosed in the range of 100 to 250 mg tapentadol twice daily. The dose was titrated to achieve sufficient pain relief to continue with effective analgesia for as long as the participant tolerated and wishes to continue treatment.
Overall Study STARTED	31
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	31

Reasons for withdrawal

Reasons for withdrawal
Measure	Tapentadol Prolonged Release All participants from the KF5503/15 that enrolled into this trial were on tapentadol prolonged release. Participants were dosed in the range of 100 to 250 mg tapentadol twice daily. The dose was titrated to achieve sufficient pain relief to continue with effective analgesia for as long as the participant tolerated and wishes to continue treatment.
Overall Study Adverse Event	5
Overall Study Death	7
Overall Study Lack of Efficacy	5
Overall Study Physician Decision	4
Overall Study Withdrawal by Subject	6
Overall Study Sponsor Decision Administrative Reasons	2
Overall Study Other	2

Baseline Characteristics

Tapentadol in Chronic Malignant Tumour Related Pain

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tapentadol Prolonged Release n=31 Participants All participants from the KF5503/15 that enrolled into this trial were on tapentadol prolonged release. Participants were dosed in the range of 100 to 250 mg tapentadol twice daily. The dose was titrated to achieve sufficient pain relief to continue with effective analgesia for as long as the participant tolerated and wishes to continue treatment.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	25 Participants n=5 Participants
Age, Categorical >=65 years	6 Participants n=5 Participants
Age, Continuous	55.8 years STANDARD_DEVIATION 11.91 • n=5 Participants
Sex: Female, Male Female	16 Participants n=5 Participants
Sex: Female, Male Male	15 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	31 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment Serbia	6 participants n=5 Participants
Region of Enrollment Hungary	4 participants n=5 Participants
Region of Enrollment Poland	5 participants n=5 Participants
Region of Enrollment Romania	5 participants n=5 Participants
Region of Enrollment Russian Federation	3 participants n=5 Participants
Region of Enrollment Bulgaria	2 participants n=5 Participants
Region of Enrollment Moldova, Republic of	6 participants n=5 Participants
Weight	64.6 kilograms STANDARD_DEVIATION 16.45 • n=5 Participants
Height	165.0 centimeters STANDARD_DEVIATION 10.24 • n=5 Participants
Body Mass Index	23.6 kg/m^2 STANDARD_DEVIATION 4.79 • n=5 Participants
Pain type Neuropathic	23 participants n=5 Participants
Pain type Visceral	22 participants n=5 Participants
Pain type Nociceptive (somatic)	26 participants n=5 Participants

PRIMARY outcome

Timeframe: Day 1; up to 144 weeks

Population: Safety Set.

Outcome measures

Outcome measures
Measure	Number of Treatment Emergent Adverse Events n=31 Participants All participants from the KF5503/15 that enrolled into this trial were on tapentadol prolonged release. Participants were dosed in the range of 100 to 250 mg tapentadol twice daily. The dose was titrated to achieve sufficient pain relief to continue with effective analgesia for as long as the participant tolerated and wishes to continue treatment.
Severity of Adverse Events mild intensity	3 participants
Severity of Adverse Events moderate intensity	15 participants
Severity of Adverse Events severe intensity	12 participants

PRIMARY outcome

Timeframe: Day 1; up to 144 weeks

Population: Safety Set.

Participant-based analysis of treatment emergent adverse events (TEAEs) regarding the relationship to the study drug (tapentadol). The TEAEs were reported by the participants or were captured by the investigator. The relationship was rated by the investigator. The categorization of relatedness into one of the two categories was based on the following: Related included "possible", "probable/likely", and "certain"; whilst unrelated treatment emergent adverse events include those rated by the investigator as "unlikely", "conditional/unclassified", "un-assessable/unclassifiable", and "not related".

Outcome measures

Outcome measures
Measure	Number of Treatment Emergent Adverse Events n=31 Participants All participants from the KF5503/15 that enrolled into this trial were on tapentadol prolonged release. Participants were dosed in the range of 100 to 250 mg tapentadol twice daily. The dose was titrated to achieve sufficient pain relief to continue with effective analgesia for as long as the participant tolerated and wishes to continue treatment.
Relatedness Assessment of Treatment Emergent Adverse Events No Treatment Emergent Adverse Events	1 participants
Relatedness Assessment of Treatment Emergent Adverse Events All Treatment Emergent Adverse Events	30 participants
Relatedness Assessment of Treatment Emergent Adverse Events Investigator-rated Related	6 participants
Relatedness Assessment of Treatment Emergent Adverse Events Investigator-rated Not Related	24 participants

PRIMARY outcome

Timeframe: Day 1; up to 144 weeks

Population: Safety Set.

Participant-based analysis of treatment emergent adverse events (TEAEs) regarding countermeasure to the study drug (tapentadol). The TEAEs were reported by the participants or were captured by the investigator. The countermeasure taken by the investigator were reported.

Outcome measures

Outcome measures
Measure	Number of Treatment Emergent Adverse Events n=31 Participants All participants from the KF5503/15 that enrolled into this trial were on tapentadol prolonged release. Participants were dosed in the range of 100 to 250 mg tapentadol twice daily. The dose was titrated to achieve sufficient pain relief to continue with effective analgesia for as long as the participant tolerated and wishes to continue treatment.
Countermeasures Taken Due to Treatment Emergent Adverse Events All Treatment Emergent Events	30 participants
Countermeasures Taken Due to Treatment Emergent Adverse Events No Treatment Emergent Adverse Events	1 participants
Countermeasures Taken Due to Treatment Emergent Adverse Events No countermeasures taken	5 participants
Countermeasures Taken Due to Treatment Emergent Adverse Events Countermeasures with Medication	17 participants
Countermeasures Taken Due to Treatment Emergent Adverse Events Trial Discontinued Countermeasure	6 participants
Countermeasures Taken Due to Treatment Emergent Adverse Events Other Countermeasure due to Somnolence	1 participants
Countermeasures Taken Due to Treatment Emergent Adverse Events Other Countermeasure due to Migraine	1 participants

PRIMARY outcome

Timeframe: Day 1; 144 weeks

Population: No evaluation was performed.

The onset and duration of TEAEs was not evaluated for this trial.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 1; up to 144 weeks

Population: The modal dose is based on assessment of the consecutive morning and evening intake amounts on each day and evaluation of the total daily dose. No participant received more than 500 mg per day.

Summary of the modal total daily dose during the treatment period. The modal dose was based on assessment of the consecutive morning and evening intake amounts on each day and evaluation of the total daily dose.

Outcome measures

Outcome measures
Measure	Number of Treatment Emergent Adverse Events n=31 Participants All participants from the KF5503/15 that enrolled into this trial were on tapentadol prolonged release. Participants were dosed in the range of 100 to 250 mg tapentadol twice daily. The dose was titrated to achieve sufficient pain relief to continue with effective analgesia for as long as the participant tolerated and wishes to continue treatment.
Assess Consumption of Tapentadol During Long Term Use less than 200 mg/day	0 participants
Assess Consumption of Tapentadol During Long Term Use 200 to less than 250 mg/day	3 participants
Assess Consumption of Tapentadol During Long Term Use 250 to less than 300 mg/day	1 participants
Assess Consumption of Tapentadol During Long Term Use 300 to less than 350 mg/day	8 participants
Assess Consumption of Tapentadol During Long Term Use 350 to less than 400 mg/day	0 participants
Assess Consumption of Tapentadol During Long Term Use 400 to less than 450 mg/day	11 participants
Assess Consumption of Tapentadol During Long Term Use 450 to less than 500 mg/day	0 participants
Assess Consumption of Tapentadol During Long Term Use 500 mg/day	8 participants

SECONDARY outcome

Timeframe: Day 1; up to 144 weeks

Population: Safety Set.

The number of days that participants took tapentadol prolonged release. The extent of exposure was categorized into 2 periods, less than 90 days and more than 90 days (up to 144 weeks).

Outcome measures

Outcome measures
Measure	Number of Treatment Emergent Adverse Events n=31 Participants All participants from the KF5503/15 that enrolled into this trial were on tapentadol prolonged release. Participants were dosed in the range of 100 to 250 mg tapentadol twice daily. The dose was titrated to achieve sufficient pain relief to continue with effective analgesia for as long as the participant tolerated and wishes to continue treatment.
Tapentadol Prolonged Release Exposure 0 to 90 days	11 participants
Tapentadol Prolonged Release Exposure more than 90 days	20 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 1; up to Week 144

Population: Safety Set.

The participant scored their pain intensity on an 11-point Numerical Rating Scale (NRS) where a score of 0 indicated "no pain" and a score of 10 indicated "pain as bad as you can imagine". Average pain intensity score is the average of pain experienced for previous 24 hours as rated on an 11-point NRS at each visit. Calculations are based on 3 consecutive planned (at 4-weekly intervals) visits. All available data of a participant was used; if a participant dropped-out or had incomplete data during a 12-week period no imputations were performed for the missing values.

Outcome measures

Outcome measures
Measure	Number of Treatment Emergent Adverse Events n=31 Participants All participants from the KF5503/15 that enrolled into this trial were on tapentadol prolonged release. Participants were dosed in the range of 100 to 250 mg tapentadol twice daily. The dose was titrated to achieve sufficient pain relief to continue with effective analgesia for as long as the participant tolerated and wishes to continue treatment.
Average Pain Intensity (Over a Twelve-week Period) Baseline	3.3 units on a scale Standard Deviation 1.79
Average Pain Intensity (Over a Twelve-week Period) Week 1 to 12	3.1 units on a scale Standard Deviation 1.95
Average Pain Intensity (Over a Twelve-week Period) Week 13 to 24	3.1 units on a scale Standard Deviation 2.51
Average Pain Intensity (Over a Twelve-week Period) Week 25 to 36	2.1 units on a scale Standard Deviation 1.57
Average Pain Intensity (Over a Twelve-week Period) Week 37 to 48	2.0 units on a scale Standard Deviation 1.71
Average Pain Intensity (Over a Twelve-week Period) Week 49 to 60	2.0 units on a scale Standard Deviation 1.78
Average Pain Intensity (Over a Twelve-week Period) Week 61 to 72	2.0 units on a scale Standard Deviation 1.61
Average Pain Intensity (Over a Twelve-week Period) Week 73 to 84	2.4 units on a scale Standard Deviation 1.97
Average Pain Intensity (Over a Twelve-week Period) Week 85 to 96	3.1 units on a scale Standard Deviation 3.16
Average Pain Intensity (Over a Twelve-week Period) Week 97 to 108	3.1 units on a scale Standard Deviation 3.76
Average Pain Intensity (Over a Twelve-week Period) Week 109 to 120	3.3 units on a scale Standard Deviation 2.52
Average Pain Intensity (Over a Twelve-week Period) Week 121 to 132	1.0 units on a scale Standard Deviation 0
Average Pain Intensity (Over a Twelve-week Period) Week 133 to 144	1.0 units on a scale Standard Deviation 0

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 1; up to 144 weeks

Population: Safety Set.

The Total Daily Dose (TDD) on any given day is the sum of the morning and evening intake amounts. The average TDD is an individuals average over the trial period.

Outcome measures

Outcome measures
Measure	Number of Treatment Emergent Adverse Events n=31 Participants All participants from the KF5503/15 that enrolled into this trial were on tapentadol prolonged release. Participants were dosed in the range of 100 to 250 mg tapentadol twice daily. The dose was titrated to achieve sufficient pain relief to continue with effective analgesia for as long as the participant tolerated and wishes to continue treatment.
Average Daily Total Tapentadol Prolonged Release Dose	360 mg per day Standard Deviation 91.21

Adverse Events

Tapentadol Prolonged Release

Serious events: 14 serious events

Other events: 30 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Tapentadol Prolonged Release n=31 participants at risk All participants from the KF5503/15 that enrolled into this trial were on tapentadol prolonged release. Participants were dosed in the range of 100 to 250 mg tapentadol twice daily. The dose was titrated to achieve sufficient pain relief to continue with effective analgesia for as long as the participant tolerated and wishes to continue treatment.
Metabolism and nutrition disorders hypoalbuminaemia	3.2% 1/31 • One participant was treated up to 144 weeks.
Renal and urinary disorders azotaemia	3.2% 1/31 • One participant was treated up to 144 weeks.
Respiratory, thoracic and mediastinal disorders hypoxia	3.2% 1/31 • One participant was treated up to 144 weeks.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) malignant neoplasm progression	29.0% 9/31 • One participant was treated up to 144 weeks.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) breast cancer	3.2% 1/31 • One participant was treated up to 144 weeks.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) metastases to lung	3.2% 1/31 • One participant was treated up to 144 weeks.
Blood and lymphatic system disorders anaemia	3.2% 1/31 • One participant was treated up to 144 weeks.
Hepatobiliary disorders cholecystitis	3.2% 1/31 • One participant was treated up to 144 weeks.
Infections and infestations pneumonia	3.2% 1/31 • One participant was treated up to 144 weeks.
Cardiac disorders cardiac failure	3.2% 1/31 • One participant was treated up to 144 weeks.

Other adverse events

Other adverse events
Measure	Tapentadol Prolonged Release n=31 participants at risk All participants from the KF5503/15 that enrolled into this trial were on tapentadol prolonged release. Participants were dosed in the range of 100 to 250 mg tapentadol twice daily. The dose was titrated to achieve sufficient pain relief to continue with effective analgesia for as long as the participant tolerated and wishes to continue treatment.
Metabolism and nutrition disorders Hypoalbuminaemia	6.5% 2/31 • One participant was treated up to 144 weeks.
Hepatobiliary disorders Hepatic function abnormal	6.5% 2/31 • One participant was treated up to 144 weeks.
Investigations Alanine aminotransferase increased	6.5% 2/31 • One participant was treated up to 144 weeks.
Investigations Aspartate aminotransferase increased	6.5% 2/31 • One participant was treated up to 144 weeks.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) malignant neoplasm progression	16.1% 5/31 • One participant was treated up to 144 weeks.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to bone	12.9% 4/31 • One participant was treated up to 144 weeks.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) neoplasm progression	9.7% 3/31 • One participant was treated up to 144 weeks.
Gastrointestinal disorders nausea	29.0% 9/31 • One participant was treated up to 144 weeks.
Gastrointestinal disorders constipation	12.9% 4/31 • One participant was treated up to 144 weeks.
Gastrointestinal disorders abdominal pain upper	6.5% 2/31 • One participant was treated up to 144 weeks.
General disorders pyrexia	12.9% 4/31 • One participant was treated up to 144 weeks.
Gastrointestinal disorders ascites	6.5% 2/31 • One participant was treated up to 144 weeks.
General disorders general physical health deterioration	9.7% 3/31 • One participant was treated up to 144 weeks.
General disorders fatigue	6.5% 2/31 • One participant was treated up to 144 weeks.
Nervous system disorders dizziness	9.7% 3/31 • One participant was treated up to 144 weeks.
Nervous system disorders headache	9.7% 3/31 • One participant was treated up to 144 weeks.
Nervous system disorders somnolence	6.5% 2/31 • One participant was treated up to 144 weeks.
Cardiac disorders sinus tachycardia	9.7% 3/31 • One participant was treated up to 144 weeks.
Cardiac disorders tachycardia	9.7% 3/31 • One participant was treated up to 144 weeks.
Infections and infestations bronchitis	6.5% 2/31 • One participant was treated up to 144 weeks.
Infections and infestations urinary tract infection	6.5% 2/31 • One participant was treated up to 144 weeks.
Musculoskeletal and connective tissue disorders pathological fracture	6.5% 2/31 • One participant was treated up to 144 weeks.
Renal and urinary disorders haematuria	6.5% 2/31 • One participant was treated up to 144 weeks.
Blood and lymphatic system disorders Anaemia	16.1% 5/31 • One participant was treated up to 144 weeks.
Blood and lymphatic system disorders Thrombocytopenia	9.7% 3/31 • One participant was treated up to 144 weeks.
Blood and lymphatic system disorders Lymphadenopathy	6.5% 2/31 • One participant was treated up to 144 weeks.

Additional Information

Director Clinical Trials

Grünenthal GmbH

Phone: +49 241 569

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Sponsor reserves the right to review any publication pertaining to the trial before it is submitted for publication. Neither party has the right to prohibit publication unless publication can be shown to affect possible patent rights.
Publication restrictions are in place

Restriction type: OTHER